The present application is directed to novel antidiabetic compounds.
The causes of Type I and Type II diabetes are still unknown, although both genetic and environmental factors seem to be involved. Type I diabetes (or insulin-dependent diabetes) is an autonomic immune disease in which the responsible autoantigen is still unknown. Patients with Type I diabetes need to take insulin intravenously to survive. Type II diabetes (formerly referred to as non-insulin dependent diabetes) is a metabolic disorder resulting from the body""s inability either to make a sufficient amount of insulin or to properly use the insulin that is produced. Insulin secretion and insulin resistance are considered the major metabolic defects, but the precise genetic factors involved remain unknown.
Patients with diabetes usually have one or more of the following defects:
Under-production of insulin by the pancreas
Over-secretion of glucose by the liver
Defects in glucose transporters
Desensitization of insulin receptors
Defects in metabolic breakdown of polysaccharides
In addition to the IV administration of insulin, currently available medications used for diabetes include 4 classes of oral hypoglycemic agents listed in the following table.
As is apparent from the above table, there are disadvantages to each of the currently available agents for use in the treatment of diabetes. Accordingly, there is a continuing interest in the identification and development of new agents, particularly orally administered, water-soluble agents that can be used for the treatment of diabetes.
Compounds having the general formula (I)-(III) have glucose-lowering activity. 
Stereocenters (designated by *) could be Rxe2x80x94 or Sxe2x80x94.
Each bond represented by dotted lines could be a double or a single bond, and the geometry across the bond could be E or Z.
R and Rxe2x80x2 are independently H or C1-C20 linear or branched alkyl or alkenyl groups that may be substituted, or functional groups like COOR3, where R3=H, a cation C1-C20 linear or branched alkyl or C5-C10 aryl; CONR1R2, where R1 and R2 may be independently or together H, linear or branched C1-C20 alkyl or C5-C20 aryl, NH2, OH, C1-C20 linear or branched alkoxy, halo, cyano, or R+Rxe2x80x2=O.
A, Axe2x80x2, Axe2x80x3, and C are independently H, C1-C20 acylamino, C1-C20 acyloxy, linear or branched C1-C20 alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 linear or branched alkoxy; C1-C20 linear or branched alkylamino, C1-C20 alkylcarboxylamino, C1-C20 carbalkoxy; carboxyl, cyano, halo, hydroxy; and n, m, and p and v are independently integers from 0 to 3;
B, Bxe2x80x2, and Bxe2x80x3 are independently H, C1-C20 acylamino, C1-C20 acyloxy; C1-C20 linear or branched alkanoyl, C1-C20 linear or branched alkenyl, C1-C20 alkoxycarbonyl, C1-C20 linear or branched alkoxy; C1-C20 linear or branched alkyl amino, C1-C20 alkyl carboxyl amino, C1-C20 carbalkoxy; aroyl, araalkanoyl, carboxyl, cyano, halo, hydroxy; and q, r and s are independently integers from 0 to 3;
Rxe2x80x3, Rxe2x80x2xe2x80x3 and Rxe2x80x3xe2x80x3 are independently H, C1-C20 linear or branched alkyl or alkenyl groups which may contain substituents, COOH, C1-C20 alkoxycarbonyl, NH2, CONH2, C1-C20 acylamino, OH, C1-C20 alkoxy, halo, or cyano.
Xxe2x95x90NH, O, S, Sxe2x95x90O, or SO2. 
Stereocenters (designated by *) could be Rxe2x80x94 or Sxe2x80x94.
Each bond represented by the dotted line could be a double or a single bond, and the geometry across it may be E or Z.
A, Axe2x80x2, and C are independently H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 alkoxycarbonyl, C1-C20 alkoxy, C1-C20 linear or branched alkyl amino, C1-C20 alkylcarboxylamino, C1-C20 carbalkoxy; carboxyl, cyano, halo, hydroxy; and t, u, and w are independently integers from 0 to 3;
B and Bxe2x80x2 are independently H, C1-C20 acylamino, C1-C20 acyloxy; C1-C20 alkanoyl, C1-C20 alkenoyl, C1-C20 alkenyl, C1-C20 alkoxycarbonyl, C1-C20 linear or branched alkoxy, C1-C20 linear or branched alkyl amino, C1-C20 alkylcarboxylamino, C1-C20 carbalkoxy, C6-C20 aroyl, C6-C20 araalkanoyl, carboxyl, cyan, halo, hydroxy; and x and y are independently integers from 0 to 3;
Rxe2x80x2, Rxe2x80x3, and Rxe2x80x2xe2x80x3 are independently H or C1-C20 linear or branched alkyl or alkenyl groups which may contain substituents, COOH, C1-C20 alkoxycarbonyl, NH2, CONH2, C1-C20 acylamino, C1-C20 alkoxycarbonyl, OH, C1-C20 alkoxy, halo or cyano.
Xxe2x95x90NH, O, S, Sxe2x95x90O, or SO2 
Stereocenters (designated by *) could be Rxe2x80x94 or Sxe2x80x94.
The bond represented by the dotted line could be a double or a single bond, and the geometry across it may be E or Z.
A and C are independently H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 linear or branched alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 linear or branched alkoxy, C1-C20 linear or branched alkyl amino, C1-C20 alkylcarboxylamino, C1-C20 carbalkoxy; carboxyl, cyano, halo, hydroxy; thiol, SOR or SOR2; and f and g are independently integers from 0 to 3;
B is independently H, C1-C20 acylamino, C1-C20 acyloxy; C1-C20 linear or branched alkanoyl, C1-C20 linear or branched alkenoyl, C1-C20 linear or branched alkenyl, C1-C20 alkoxycarbonyl, C1 -C20 linear or branched alkoxy, C1-C20 linear or branched alkyl amino, C1-C20 alkylcarboxylamino, C1-C20 carbalkoxy, C5-C20 aroyl, C6-C20 araalkanoyl, carboxyl, cyan, halo, hydroxy; and e is an integer from 1 to 3;
Rxe2x80x2, Rxe2x80x3, and Rxe2x80x2xe2x80x3 are independently H or C1-C20 linear and branched alkyl or alkenyl groups which may contain substituents, COOH, C1-C20 alkoxycarbonyl, NH2, CONH2, C1-C20 acylamino, C1-C20 alkoxycarbonyl, OH, C1-C20 alkoxy, halo, cyano.